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Resveratrol fails to affect cocaine conditioned place preference behavior, but alleviates anxiety-like behaviors in cocaine withdrawn rats

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Abstract

Rationale

Resveratrol participates in regulating abnormal behaviors in psychostimulant-exposed animals.

Objectives

To examine effects of resveratrol on relapse and anxiety-like behaviors in cocaine withdrawn rats and to investigate possible molecular mechanisms underlying resveratrol effects in hippocampus (HP) and prefrontal cortex (PFC).

Methods

Conditioned place preference (CPP) assay and elevated plus maze (EPM) test were used to examine cocaine CPP behavior and anxiety-like behaviors in rats, respectively. Resveratrol was administrated to cocaine withdrawn rats. Levels of MDA, GSH and SOD were examined to evaluate oxidative status, and levels of IL-6, IL-1β and TNF α were measured to examine inflammatory status and levels of caspase-3 and BAX was examined to evaluate apoptotic status in HP and PFC. SIRT expression was also examined here.

Results

Resveratrol did not affect cocaine CPP behaviors, but attenuated anxiety-like behaviors in cocaine withdrawn rats. Levels of MDA and TNFα in PFC, and levels of MDA, SOD, GSH, IL-6, IL-1β, TNFα, caspase-3 and BAX in HP, but not SIRT1 expression in both regions were significantly changed during cocaine withdrawal period. Except SOD, resveratrol reversed above neurochemical changes induced by cocaine withdrawal. Furthermore, RSV induced a greater upregulation of SIRT1 expression in PFC in cocaine withdrawn rats than that in saline controls.

Conclusions

Current findings suggest that resveratrol may influence behaviors in cocaine withdrawn rats. Oxidative stress, inflammation, apoptosis, and SIRT1 signaling pathway in HP or PFC might be involved in mediating effects of RSV on behaviors in cocaine withdrawn rats.

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Abbreviations

CAS3:

Caspase-3

CPP:

Conditioned place preference

EPM:

Elevated plus maze

GSH:

Glutathione

HP:

Hippocampus

IL-1β:

Interleukin 1β

IL-6:

Interleukin 6

MDA:

Malondialdehyde

PFC:

Prefrontal cortex

RSV:

Resveratrol

SIRT1:

Sirtunin1

SOD:

Superoxide dismutase

TNF α:

Tumor necrosis factor α

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81571303, No. 81371467, No. 81000572) and Natural Science Foundation of Jiangsu Province (No. 10KJB180005).

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    Authors and Affiliations

    1. Department of Human Anatomy, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China

      Panpan Hu, Wei Zhu & Xiaowei Guan

    2. Department of Pharmacology, Nanjing Medical University, Nanjing, China

      Chao Zhu & Lai Jin

    3. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

      Yun Guan

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    1. Panpan Hu
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    Correspondence to Xiaowei Guan.

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    Panpan Hu and Wei Zhu contributed equally to this work.

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    Hu, P., Zhu, W., Zhu, C. et al. Resveratrol fails to affect cocaine conditioned place preference behavior, but alleviates anxiety-like behaviors in cocaine withdrawn rats. Psychopharmacology 233, 1279–1287 (2016). https://doi.org/10.1007/s00213-016-4210-4

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    • DOI: https://doi.org/10.1007/s00213-016-4210-4

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